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Abstract

Background

This study aimed to document the outcome dimensions that physicians see as important
in defining cure from depression. The study also aimed to analyse physicians' attitudes
about depression and to find out whether they affect their prescribing practices and/or
the outcome dimensions that they view as important in defining cure.

Methods

A 51-item questionnaire based on six validated scales was used to rate the importance
of several depression outcome dimensions. Physicians' attitudes about depression were
also assessed using the Depression Attitude Scale. Overall, 369 Belgian physicians
(264 general practitioners [GPs]; 105 psychiatrists) participated in the DEsCRIBE™ survey.

Results

GPs and psychiatrists strongly agreed that functioning and depressive symptomatology
were most important in defining cure; anxious and somatic symptomatology was least
important. GPs and psychiatrists differed in their attitudes about depression (p < 0.001). Logistic regression revealed that the attitudes of GPs - but not psychiatrists
- were significantly associated with their rates of antidepressant prescription (p
< 0.001) and that certain attitudes predicted which outcome dimensions were seen as
important in defining cure.

Conclusions

Belgian GPs and psychiatrists strongly agreed on which criteria were important in
defining cure from depression but differed in their attitudes about depression. The
outcome dimensions that were considered important in defining cure were influenced
by physicians' attitudes - this was more pronounced in GPs than in psychiatrists.

Background

In 2006, the US National Institute of Mental Health published an article regarding
the possibility of finding a cure for mental disorders [1]. This paper was a call to health practitioners to set themselves more ambitious goals
when treating patients with mental illness. Moreover, this initiative aimed to cause
a paradigm shift in perceptions of depression and its cure. While such an effort is
admirable the paper failed to take into account the complexity of mental disorders
such as depression and the inadequacies in our current ability to monitor and define
the disease. Depression is multifactorial, and its aetiology and presentation differ
greatly from one patient to the next. Furthermore, decades of research have failed
to find consistent biological markers for depression or for its outcomes. To date,
clinical and sociodemographic characteristics, such as comorbid anxiety, age or employment
status, are the most consistent prognostic factors in depression [2,3], while evaluation of outcomes in depression has been limited to changes in symptom
severity and concepts such as response, remission, recovery, relapse and recurrence
[4,5]. Remission is usually defined as a score of less or equal to 7 on the Hamilton Depression
Rating Scale (17 item version) or less or equal to 10 on the Montgomery-Asberg Depression
Rating Scale: remission is therefore defined only on the basis of absence of symptoms.

In reality, most patients with depression present with comorbid somatic symptoms [6] or anxiety often reaching a severity akin to that of an anxiety disorder or a somatoform
disorder [7]. A recent study of patients with major depressive disorder has illustrated that these
symptom clusters (pain, anxiety and depression) are important in patients' assessment
of improvement [8]. Patients reportedly value symptom resolution, normalisation of function and quality
of life (QoL) when assessing whether their depression has remitted [9,10].

Additional evidence suggests that current definitions of outcome are inadequate. For
example, although many psychiatrists believe anhedonia to be a core symptom of depression,
assessment of change during the treatment of depression is usually limited to a decrease
in negative affect, while an increase in positive affect is neglected. Furthermore,
although the Diagnostic and Statistical Manual of Mental Disorders (fourth edition)
definition of major depressive disorder includes a functional criterion (i.e., symptoms
cause clinically significant distress or impairment in social, occupational or other
important areas of functioning), functioning is often neglected in the inclusion criteria
and the outcome measures of randomised controlled trials (RCTs). In order to address
the limitations of existing outcome measures, a number of published papers have begun
to address the importance of QoL in quantifying patients' response to antidepressant
treatment [11,12]. QoL potentially represents a generic, global outcome measure that allows comparison
of treatment effects across different disorders.

While we assert that the current narrow outcome definitions in the treatment of depression
present only the view of the medical field instead of the outcomes that matter most
to patients, there is presently a paucity of published data on patients' views of
what constitutes a good outcome in depression [13,10]. Moreover, the views of individual physicians on the different dimensions that are
important in defining a good outcome are also poorly documented. Kerr and colleagues
[14] have reported that the attitudes of general practitioners [GPs] and psychiatrists
towards depression and the treatment of depression differ markedly and also determine
their prescribing practice and treatment outcomes. It is therefore expected that the
attitudes of GPs and psychiatrists are also likely to differ about how to define satisfactory
outcomes in depression treatment.

PROact® (PRognosis Optimisation by adequate customised therapy) is an initiative that aims
to define cure from depression by creating a therapeutic contract between patients
and physicians. This paper documents the first part of PROact® - DEsCRIBE™ (DEfinition of the CRIteria of BEing cured). In DEsCRIBE™ physicians were
asked to consider what they thought was important in defining cure in patients with
depression. In addition, we analysed the attitudes of GPs and psychiatrists concerning
depression and whether their attitudes affect their prescribing practices and/or predict
the outcome dimensions that are ranked highest when defining cure from depression.

Methods

Study design

This study was conducted between March and August 2009. The Belgian Central Medical
Database was used to select a random sample of GPs and psychiatrists. These physicians
were contacted between March and July 2009 by randomly assigned Lundbeck Belgium sales
representatives who asked about their willingness to participate in the study. Any
physician who declined to participate was replaced with another physician drawn randomly
from the Central Medical Database.

Physicians who agreed to participate were asked to complete a two-part, password-protected,
electronic web-based questionnaire. Part I included questions regarding their demographic
characteristics, clinical experience and a query about whether they prescribe antidepressants
to ≤ 50% (low prescribers) or > 50% (high prescribers) of their patients with depression.
Part I also required participants to complete the Depression Attitude Scale (DAS)
[15] which consists of 20 statements regarding the physician's attitudes about depression
and its treatment. Physicians were asked to rate their agreement with each statement
of the DAS on a 5-point Likert scale (where 1 = strongly agree and 5 = strongly disagree).

Statistical analysis

Results were summarised as mean and standard deviation (SD) for quantitative variables
and scores; frequency tables were used for categorical findings. Mean values were
compared by one-way analysis of variance and proportions were analysed by the chi-squared
test. The 51 DEsCRIBE™ questionnaire items were ranked by decreasing mean score (i.e.,
by order of importance) both for the whole sample and for GPs and psychiatrists separately.
Spearman's rank correlation coefficients were calculated to measure the association
between the attitude statements. A factor analysis based on the maximum likelihood
principle and with varimax rotation was applied separately to the attitude statements
of GPs and psychiatrists. This method allows selecting the exact number of factors
which explain at least 100% of the common variance. These factors were subsequently
analysed with respect to the demographic features and prescribing behaviour of the
physician (high vs. low prescribers).

The association between the attitude factors and the six DEsCRIBE™ outcome dimensions
was also studied by multiple regression analysis. Logistic regression was used to
assess the relationship between the prescribing pattern of the physician (high vs
low) and the attitude factors. The association with each factor was expressed in terms
of the odds ratio (OR) and its 95% confidence interval (CI). Results were considered
statistically significant at the 5% level (p < 0.05). Calculations were performed
using SAS (version 9.1 for Windows) and S-PLUS (version 6.1) statistical packages.

Results

Study population

In total, 1240 physicians were contacted, of whom 369 completed the survey (response
rate of 30%). The characteristics of the physicians who completed the survey and of
the general Belgian physician population are compared in Table 1. The mean age of the participating physicians and of the Belgian physician population
were comparable, while the proportion of female physicians was 7-14% lower in the
study population vs. the Belgian physician population.

Defining a patient who is cured of depression

Physicians were asked to rate the importance of each of the 51 items of the multidimensional
DEsCRIBE™ questionnaire in defining cure. Among the PHQ-9 depressive symptoms, GPs
and psychiatrists considered decreased interest, depressed mood and suicidal ideation
to be most important in defining cure, whereas concentration, appetite and psychomotor
retardation/agitation were considered to be least important (Table 2).

Table 2. Ranking of the nine items of the PHQ-9 depressive symptomatology outcome dimension
in terms of their importance in defining cure from depression according to GPs and
psychiatrists

GPs and psychiatrists agreed strongly about the items that were most and least important
in defining cure from depression (Table 3). The top 10 items for GPs and psychiatrists comprised 3 PHQ-9 depression items,
3 WHOQOL-BREF items, 2 SDS items and 2 PANAS-pos items. The 10 least important items
were all PHQ-somatic items.

Table 3. Most and least important statements in defining cure in patients with depression

The ranking of the mean scores for the six scales was identical for GPs and psychiatrists,
with the SDS and PHQ-9 depression scales considered the two most important scales
in defining cure and the HADS-A and PHQ-somatic considered the two least important
scales (Table 4).

Table 4. Importance of scales for assessing whether a patient has been cured of depression

Physicians' attitudes about depression

Highly significant differences (p ≤ 0.001) were found between the attitudes of GPs
and psychiatrists for 10 of the 20 statements on the DAS (Table 5). Several relations were noted between some DAS statements. For example, "feeling
comfortable treating patients with depression" (A9) and "finding the experience rewarding"
(A15) were positively correlated in both groups of physicians (r = 0.33, p < 0.001
for GPs and r = 0.34, p < 0.001 for psychiatrists). It is interesting to note that
GPs (but not psychiatrists) who are comfortable treating patients with depression
(A9) and find it rewarding (A15) did not agree that an underlying biochemical abnormality
is causative for severe cases of depression (A4) (r = -0.13, p < 0.05) and did not
agree that psychotherapy tends to be unsuccessful in patients with depression (A16)
(r = -0.13, p < 0.05). It is also interesting to note that psychiatrists (but not
GPs) who agree that a nurse could be useful in supporting patients with depression
(A11) disagree that depression reflects a characteristic response in patients that
is not amenable to change (A10) (r = -0.29, p < 0.01).

Table 5. Depression Attitude Scale questionnaire results - only statements with a significant
difference between GPs and psychiatrists are shown

A maximum likelihood (with varimax rotation) factor analysis of the DAS responses
was performed separately for GPs and psychiatrists (Table 6). The analysis of GP responses revealed a three-factor solution. The factors were
named after the statement with the highest loading (coefficient) within each factor:

Table 6. Factor analysis of Depression Attitude Scale statements in GPs and psychiatrists -
only attitude statement with at least one loading ≥ 40 or ≤ -40 for any of the factors
are represented

■ Factor 1: Depression is how people with poor stamina deal with stress.

■ Factor 2: It is rewarding looking after patients with depression.

■ Factor 3: Depression has a poor outcome.

By contrast, the analysis of psychiatrist responses revealed a five-factor solution.
Three of these factors (Factors 1 to 3) were basically the same as those identified
for GPs as the statements with the highest loading in Factors 1, 2 and 3 were the
same for the psychiatrist and GP groups. The two additional factors for psychiatrists
were:

Comparison of the scores for the five factors between the two physician groups revealed
that, compared with psychiatrists, GPs believe more strongly that depression is how
people with poor stamina deal with stress (Factor 1; p < 0.0001) and that GPs feel
it is less rewarding treating patients with depression (Factor 2; p < 0.0001). Moreover,
GPs believe that there is little to offer to patients with depression who do not respond
to treatment by GPs, but to a lesser extent than psychiatrists (Factor 3; p < 0.0001)
and more strongly disagree that treating depression is the role of the psychiatrist
(Factor 4; p < 0.0001). Compared with psychiatrists, GPs agree more with the statement
that most depressive disorders in a primary care practice do not improve without medication
and they disagree less with the statement that freely available psychotherapy would
be more beneficial than antidepressants (Factor 5; p < 0.0001).

Physician attitudes about depression and prescribing patterns

The present survey indicated that more psychiatrists than GPs are high prescribers
of antidepressants - 69% of psychiatrists and 37% of GPs prescribed antidepressants
to

> 50% of their patients with depression.

A logistic regression analysis with prescribing pattern (high vs. low prescribers)
as the dependent variable and the three GP attitude factors and sociodemographic characteristics
as independent variables revealed a significant association between GPs' perceptions
and their prescribing behaviour (p = 0.0067). Specifically, low prescribing was predicted by GPs' perception that looking
after patients with depression is not rewarding (Factor 2, OR = 0.69; 95% CI: 0.49
to 0.97) and that depression has a poor outcome (Factor 3, OR = 0.62; 95% CI: 0.43
to 0.88).

A logistic regression analysis with prescribing pattern as the dependent variable
and the psychiatrists' five depression attitude factors and sociodemographic characteristics
as independent variables did not reveal any significant relationship between the depression
attitude factors of psychiatrists and their prescribing behaviour (p = 0.068).

Physician attitudes about depression and the importance of different outcome dimensions
in defining cure

Six regression analyses were performed on the psychiatrist (and GP) data in order
to assess whether the five (or three) depression attitude factors (in addition to
gender and age) predicted the relative importance of each of the six outcome dimensions
used in defining cure (ranking based on the mean score on each outcome dimension where
1 = lowest ranking and 6 = highest ranking).

A significant model was found for only two of the six outcome dimensions for psychiatrists.
Psychiatrists who attach a greater relative importance to somatic symptomatology in
defining cure agreed that it is rewarding looking after patients with depression (Factor
2; OR = 0.36; 95% CI: 0.16 to 0.82). Psychiatrists who attached a greater relative
importance to functioning in defining cure agreed that depression is how people with
poor stamina deal with stress (Factor 1; OR = 0.52; 95% CI: 0.33 to 0.81).

A significant model was found for five out of the six outcome dimensions for GPs.
GPs who attach a greater relative importance to depressive symptomatology in defining
cure agreed more strongly that depression is how people with poor stamina deal with
stress in their lives (Factor 1; OR = 0.64; 95% CI: 0.49 to 0.84). GPs who think that
anxious symptomatology is important in defining cure disagreed more strongly that
depression is how people with poor stamina deal with stress in their lives (Factor
1; OR = 1.31; 95% CI: 1.00 to 1.71) and disagreed more strongly that depression has
a poor outcome (Factor 3; OR = 1.40; 95% CI: 1.04 to 1.89). GPs who attach a greater
relative importance to functioning in defining cure agreed more strongly that depression
is how people with poor stamina deal with stress in their lives (Factor 1; OR = 0.62;
95% CI: 0.47 to 0.82) and disagreed more strongly that depression has a poor outcome
(Factor 3; OR = 1.36; 95% CI: 1.00 to 1.84). GPs who think that positive affect is
important in defining cure disagreed more strongly that depression is how people with
poor stamina deal with stress in their lives (Factor 1; OR = 1.77; 95% CI: 1.35 to
2.32). GPs who attach a greater relative importance to QoL in defining cure were more
likely to be women (OR = 1.99; 95% CI: 1.10 to 3.61) and agreed more strongly that
depression has a poor outcome (Factor 3; OR = 0.62; 95% CI: 0.46 to 0.84).

Discussion

The primary study finding was that GPs and psychiatrists give very similar responses
when asked about which depressive symptoms and broader outcome dimensions are most
important in defining cure from depression. Indeed, when the nine depression items
of the PHQ-9 were ranked by these physician groups, the three most and least important
items were identical. To the best of our knowledge this is the first documented comparison
of GPs' and psychiatrists' opinions about defining cure from depression.

The 10 most important items in defining cure comprised the PHQ-9 items of anhedonia,
depressed mood and suicidal ideation, the SDS items of occupational functioning and
social functioning, the WHO-QOL items of being able to enjoy life, being able to concentrate
and feeling life is meaningful and the PANAS-pos items of being interested and being
active. The 10 least important items were all items from the somatic symptom scale.
This is a remarkable finding as the importance of painful and non-painful symptoms
has recently received a great deal of attention in the scientific literature [2,7,16,17].

Ranking the outcomes at the dimension level gives a broader definition of what a useful
outcome in clinical practice might be. This contrasts with the narrow outcome definitions
espoused by RCTs, which tend to focus on depression scale scores, response and remission
[18]. It has been documented that patients enrolled in RCTs rarely typify the patients
seen in clinical practice [19], and our data illustrate that the concept of cure encompasses more than can be captured
by single scale scores and the current notions of response and remission. This idea
has been mooted previously in the published literature [4,20] and has been stated particularly elegantly by Linsey McGoey of the Said Business
School, University of Oxford: "Never before have the inadequacies of RCTs been so
apparent to so many. Yet equally, never before have those in positions of authority
- from regulators, to NICE policy makers, to doctors - relied so extensively on RCT
evidence" [21]. Our data are indeed an illustration of the previous statement since endpoints in
RCTs and endpoints in physicians' view seem to be very different.

The broader definition of cure from depression championed here seems to agree largely
with published data reporting what patients consider to be important in defining cure.
Patients give highest priority to positive mental health (optimism, vigour and self-confidence)
followed by feeling normal, a return to usual levels of functioning at work or at
home, feeling in emotional control, participating in and enjoying relationships with
family and friends and, finally, the absence of depressive symptoms [9].

Analysis of these broader outcome dimensions is also instructive when looking at the
concepts of relapse and recurrence. Residual deficits after treatment should not refer
only to residual symptoms, rather they should encompass impairments in social and
occupational functioning (even independently of depressive symptom scores). These
broader outcome dimensions have been reported to be significant and independent risk
factors for relapse and recurrence [22-24].

A second finding of this study were the important differences in attitudes about depression
and its treatment demonstrated by GPs and psychiatrists (as measured using the DAS).
Overall, psychiatrists have a more positive attitude towards depression and its treatment
- this has also been reported in a study based in Wales [14]. In the current study, a factor analysis gave a different solution for GPs (3 factors)
and psychiatrists (5 factors; 3 of them being the same as for the GPs). A 4-factor
solution was reported in a study of 72 GPs by Botega and colleagues [15], where 3 of the 4 factors are mainly comparable to 3 of the 5 factors reported here.
Factors I (antidepressant/psychotherapy), II (professional unease) and III (inevitable
course of depression) in the Botega paper [15] correspond with Factors 2, 3 and 5 in our sample. It is a matter of concern that
GPs feel that treating patients with depression is unrewarding (Factor 2) but it is
interesting that GPs are pessimistic about what to do if a patient does not respond
to their treatment (Factor 3) and that they feel most of their depressed patients
should be treated with antidepressants (Factor 5).

The importance of physicians' attitudes to depression and their ability to manage
this disorder effectively have been commented upon previously [14,15,25]. For example, one study [25] used a modified form of the DAS and found that non-psychiatrist physicians in Taiwan
who were positive about the treatment of depression did not display avoidant/helpless
attitudes and had the best scores in depression management. These findings support
an earlier study of GPs in Scotland that also used the DAS [26]. This study reported that pessimism associated with the treatment of depression was
linked to unwillingness to become involved with managing patients with depression,
while confidence resulted in earlier recognition of the disorder [26]. Feeling comfortable with treating depression was also linked to more accurate diagnosis
in a study of GPs in the north of England [27]. This study concluded that the accurate identification and appropriate management
of depression by GPs was not an independent variable; instead it differed with different
physicians' attitudes and skills [27].

It is perhaps unsurprising that psychiatrists are more comfortable treating patients
with depression and find the experience more rewarding than GPs as they are specialists
in this field. It has been reported that mental health expertise among GPs is also
helpful in improving their attitudes towards the treatment of depression. An earlier
study of GPs using the DAS revealed that physicians who had gained postgraduate mental
health qualifications were more optimistic about achieving positive outcomes for their
patients with depression and felt more comfortable in assisting these patients [28]. By contrast, a study of primary care physicians' attitudes to depression conducted
in Brazil illustrates that a lack of exposure to patients with depression has the
opposite effect [29]. The results of such surveys are useful as they suggest that training and experience
can influence physicians' comfort in dealing with depression. It should also be considered
that attitudes may influence participation in training programmes and influence the
patients that physicians treat within their own practice. The finding that psychiatrists'
attitudes do not appear to influence how they treat their patients is harder to explain.
Perhaps the greater experience of psychiatrists concerning mental illness leads them
to be less influenced by personal attitudes.

A third finding of this study is that compared with psychiatrists, GPs prescribe antidepressants
to a much smaller proportion of their patients with depression. This could of course
be due to lower severity of depression in the patients seen by GPs and/or by the fact
that in Belgium most patients first seek help for depression in primary care and are
often only treated by a specialist when a first-line modality has failed. However,
our data suggest that prescribing patterns are also predicted by physicians' attitudes,
although this was only the case for GPs, not psychiatrists. To the best of our knowledge,
this is a novel finding that has not been previously reported. Our study also indicates
that low prescribing in GPs (but not in psychiatrists) is predicted by the following
attitudes: that it is not rewarding to look after patients with depression (Factor
2) and that depression has a poor outcome (Factor 3). Studies regarding the relationship
between physicians' attitudes and their prescribing patterns are scarce. Botega and
colleagues [15] identified a subgroup (n = 26/72) of high-prescribing GPs. Analysis of low-dose prescribers
among GPs in a study in Wales [14] indicated that, compared with standard-dose prescribers, this group were more in
favour of psychotherapy as a treatment modality, agreed less strongly that depression
has a biological basis, and agreed less strongly that depression could be treated
effectively with antidepressants. Dowrick and colleagues [27] found that GPs' attitudes (measured using the DAS) did not predict the frequency
with which they prescribed antidepressants; however, more positive attitudes regarding
the biological basis of depression did predict the class of antidepressants that they
prescribed (selective serotonin reuptake inhibitors). The present data suggest that,
for GPs at least, finding it rewarding to look after patients with depression is correlated
with more positive attitudes towards psychotherapy and with a less strong belief in
a biological basis for depression. One could therefore speculate that these physicians
find a good doctor-patient relationship more satisfying than they do prescribing an
antidepressant.

A final finding of our study was that the outcome dimensions considered to be important
in defining cure from depression were associated with physicians' attitudes towards
depression. This result was more pronounced in GPs than in psychiatrists. It is difficult
to interpret this finding, especially as overall both physician groups agreed strongly
on the outcome dimensions that were important in defining cure. Our perception is
that this result is consistent with the earlier finding that GPs are more influenced
by their attitudes about depression than are psychiatrists. The data also suggest
female GPs attach more importance to QoL issues than their male colleagues.

As with any survey, the findings reported here are only valid for the physicians who
participated. The characteristics of physicians who declined to participate were not
described and comparison of basic demographic characteristics revealed that the survey
population consisted of a smaller percentage of women than the general Belgian physician
population. However, refusal to participate is a universal issue in observational
studies and on this issue our study was no more or less biased than any other study
of similar methodology.

Our study asked physicians to rate whether they prescribe antidepressants to ≤ 50%
or > 50% of their patients with depression. Responses to this question could be subject
to recall bias and may be influenced by physicians' attitudes. Furthermore, the types
of patients that are seen by psychiatrists and GPs differ. In Belgium, patients with
depression are initially treated by a GP who then refers patients requiring second-line
treatment to a psychiatrist. Consequently, GPs may treat more patients with depressive
adjustment disorder while psychiatrists see more patients with major depressive disorder.
The attitudes, beliefs and treatment patterns of GPs and psychiatrists are therefore
likely to vary in response to the differences in their respective patient populations.

Conclusions

The present study illustrates that (Belgian) GPs and psychiatrists strongly agree
on the criteria that are important in defining cure from depression but strongly differ
in their attitudes towards depression. Psychiatrists prescribe antidepressants to
a larger proportion of their patients with depression compared with GPs. Prescribing
patterns are significantly influenced by physicians' attitudes about depression, but
only in GPs. The outcome dimensions considered to be most important in defining cure
are also influenced by physicians' attitudes - this finding was more pronounced for
GPs than for psychiatrists. Future research should address patients' perceptions of
what defines cure and whether these attitudes correspond with those of their physician.
Such research could even assess whether convergence or divergence between physicians'
and patients' expectations about cure influences outcome or treatment satisfaction.

Competing interests

KD has served as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers
Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Servier, Takeda and Wyeth; EC has served
as a consultant for AstraZeneca, Eli Lilly and Servier and has served as a member
of speaker bureaus for AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Lundbeck and
Janssen. AA, MA and KvH have no financial or non-financial interests that may be relevant
to the submitted work. GVG is a full-time employee of Lundbeck Belgium.

Authors' contributions

All authors were involved in the analysis and interpretation of the data in this manuscript
and were involved in the drafting and revising of the manuscript for intellectual
content. All authors read and approved the final manuscript.

Acknowledgements

The PROact group is a partnership between four academic professors and Lundbeck Belgium,
Brussels, Belgium. Medical writing support was provided by Jane Bryant, PhD, of Anthemis
Consulting Ltd and was funded by Lundbeck Belgium. Jean-Manual Fontaine of Lundbeck
Belgium provided invaluable help in setting up the PROact initiative.